The primary objective of this investigation is structural elucidation and possible synthetic production of the principal skin test reactive determinant from crude histoplasmin. Previous investigation has resulted in isolation of two principal glycopeptides dII and dIII, from crude histoplasmin. The former (dII) exhibits maximal sensitivity and specificity in elicitation of delayed hypersensitivity in guinea pigs infected with Histoplasma capsulatum. The latter (dIII) elicits reactions in guinea pigs infected with either H. capsulatum or Blastomyces dermatitidis. Recent investigations have elucidated the complete amino acid compositions for histoplasmin HPD dII and dIII. The proposed studies, however, specifically involve completion of selective enzymatic and/or partial acidic degradation of these two glycopeptides and skin test evaluation of the resulting hydrolytic products. Upon obtaining the antigenic determinants of smallest possible molecular weight which will elicit delayed hypersensitivity, they in turn will be subjected to complete acidic and/or alkaline hydrolysis and respectively analyzed for amino acid sequence and carbohydrate composition. Elucidation and comparison of active antigenic determinants in the HPD dII and dIII molecules and similar future studies for other mycotic and/or bacterial antigens could allow comprehension of existing cross- reactivity (non-specificity). Complete structural elucidation and demonstrable specificity for an antigenic determinant in histoplasmin HPD dII, on the other hand, could warrant large scale production (Merrifield Solid Phase Method) of a synthetic product active in detection of delayed hypersensitivity to histoplasmosis.